Targeting the global regulator Lsr2 as a novel approach for anti-tuberculosis drug development

• Published in: Expert review of anti-infective therapy Vol. 10; no. 9; pp. 1049 - 1053
• Main Authors: Liu, Jun, Gordon, Blair RG
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.09.2012; Expert Reviews Ltd; Informa Healthcare
• Subjects: Antibiotics; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Drug Design; Drug development; Drug therapy; Gene expression; Gene Expression Regulation, Bacterial - drug effects; Genetic aspects; global regulator; H-NS; Infection; Leprosy; Lsr2; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; nucleoid-associated protein; Physiological aspects; Product development; Reviews; Transcription; Tuberculosis; Virulence; Virulence - genetics
• ISSN: 1478-7210; 1744-8336
• DOI: 10.1586/eri.12.86

Leprosy serum reactive clone 2 (Lsr2; Rv3597c) is a recently identified nucleoid-associated protein that acts as a global transcriptional regulator of Mycobacterium tuberculosis. Strikingly, Lsr2 appears to play a critical role in controlling the expression of virulence-associated genes. Here the authors outline the current knowledge concerning this novel global regulator and its potential as a target for chemotherapeutic intervention. Compounds that induce high level expression of lsr2 may lead to abolishment of virulence traits and render the bacterium incapable of causing infection and/or disease. Alternatively, compounds that either silence lsr2 expression or block the protein's function could be lethal since it has been postulated that lsr2 is essential in M. tuberculosis.